rs201401363
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS1_Supporting
The NM_016341.4(PLCE1):āc.1201T>Cā(p.Tyr401His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,210 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_016341.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCE1 | NM_016341.4 | c.1201T>C | p.Tyr401His | missense_variant | 2/33 | ENST00000371380.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCE1 | ENST00000371380.8 | c.1201T>C | p.Tyr401His | missense_variant | 2/33 | 1 | NM_016341.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000329 AC: 50AN: 152094Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000727 AC: 18AN: 247446Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134362
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1460998Hom.: 1 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 726786
GnomAD4 genome ? AF: 0.000328 AC: 50AN: 152212Hom.: 1 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74432
ClinVar
Submissions by phenotype
Nephrotic syndrome, type 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 11, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 19, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 401 of the PLCE1 protein (p.Tyr401His). This variant is present in population databases (rs201401363, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PLCE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 586318). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at